The carcinogen methylazoxymethanol (MAM) acetate induces tumors in rats predominantly of the liver and colon. Since MAM does spontaneously decompose to liberate a reactive alkylating moiety this marked organotropism is surprising and suggests that MAM might be metabolized selectively by those tissues sensitive to its effects. We have investigated the hypothesis of Schoental (Br. J. Cancer 8: 436, 1973) that MAM might be a substrate for alcohol dehydrogenase. Our results indicate that, in fact, NAD ion-dependent dehydrogenase activity using MAM as substrate is detectable in 169,000 xg supernatant fractions from liver, duodenum, cecum and colon, tissues sensitive to the acute and chronic effects of MAM acetate. Jejunum and ileum, relatively resistant to this agent, had no measureable activity. We also found that MAM is substrate for horse liver alcohol dehydrogenase and that pyrazole, an inhibitor of alcohol dehydrogenase, could prevent MAM acetate-induced acute lethality. These results suggest that the NAD ion-dependent dehydrogenase activity observed with MAM might be due to alcohol dehydrogenase. Other dehydrogenases might also be important, however, since NADP ion-dependent enzymatic activity is detectable in tissues other than liver. The importance of these reactions in the induction of tumors is being investigated. Also, the effects of other carcinogens might be influenced by NAD/NADP-dependent dyhydrogenases. In this regard Phillips, et al. (J. Natl. Cancer Inst. 58:629, 1977) reported that pyrazole decreases the metabolism and toxicity of dimethylnitrosamine. We have confirmed these findings and have extended our studies to include additional carcinogens.